title: Disruption of calmodulin-dependent protein kinase II α/brain-derived neurotrophic factor (α-CaMKII/BDNF) signalling is associated with zinc deficiency-induced impairments in cognitive and synaptic plasticity.
abstract: Maternal dietary Zn deficiency during fetal development induces substantial cognitive dysfunctions in the resultant offspring. The mechanism underlying this effect is unclear. The present study evaluated whether the impairments caused by gestational and lactational Zn deficiency are mediated by the hippocampal calmodulin-dependent protein kinase II α (α-CaMKII)/brain-derived neurotrophic factor (BDNF) signalling pathway as well as whether they can be restored by postnatal Zn supplementation. Rats were randomly divided into four groups on the first day of pregnancy (n 12): control (CO) group; pair-fed (PF) group; Zn-deprived (ZD) group; orally Zn-supplemented group. The spatial memory of the offspring was tested at postnatal day 35 using the Morris water maze. Long-term potentiation (LTP) in the rat hippocampal medial perforant path-dentate gyrus pathway was evaluated simultaneously, and α-CaMKII and BDNF protein levels were examined by Western blot analysis. The results demonstrated that the ZD group exhibited a significantly longer latency period in the Morris water maze as well as a significantly decreased LTP amplitude compared with the CO and PF groups. α-CaMKII and BDNF protein expression in the hippocampus was significantly reduced in the ZD group. Postnatal Zn supplementation restored the cognitive dysfunction induced by gestational Zn deficiency but could not completely reverse the decreased LTP and α-CaMKII/BDNF protein levels. Our findings suggest that the α-CaMKII/BDNF signalling pathway may be involved in Zn deficiency-induced cognitive and synaptic impairments.
authors.affiliation: MOE-Shanghai Key Laboratory of Children's Environmental Health, XinHua Hospital, Shanghai Jiao Tong University School of Medicine, 1665 Kong Jiang Road, Shanghai 200092, People's Republic of China.
authors.forename: XiaoDan
authors.initials: X
authors.lastname: Yu
authors.forename: Tianhong
authors.initials: T
authors.lastname: Ren
authors.forename: XiaoGang
authors.initials: X
authors.lastname: Yu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D003677:Deficiency Diseases / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D019587:Dietary Supplements; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology*; D007774:Lactation; D008297:Male; D018782:Maze Learning; D008569:Memory Disorders / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000187:drug effects; D011247:Pregnancy; D039401:Prenatal Nutritional Physiological Phenomena; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D014131:Trace Elements / Q000172:deficiency / Q000627:therapeutic use; D015032:Zinc / Q000172:deficiency* / Q000627:therapeutic use
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D014131:Trace Elements; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D015032:Zinc